Magnesium deficiency up-regulates Myod expression in rat skeletal muscle and C2C12 myogenic cells.

Magnesium (Mg) deficiency induces the production of free radicals, increases cytosolic ionized calcium concentration, and modulates the function of skeletal muscle in rats. The present study examined the effects of Mg deficiency on the gene expression of molecules related to myogenesis in the gastrocnemius muscle as well as in C2C12 myogenic cells. Ingestion of an Mg-deficient diet resulted in a lower weight of the gastrocnemius muscle and higher concentration of muscular TBARSs, an index of oxidative stress. Mg deficiency also enhanced the expression of Myod and myogenin. In vivo effects of Mg deficiency on myogenic gene expression were partially reproduced in in vitro C2C12 cells; expression of Myod was up-regulated by a mixed culture of myoblasts and myotubes with Mg-deficient medium, which related to the simultaneous up-regulation of Myhc IIb, a myotube-specific protein. The culture with Mg-deficient medium did not increase the gene transcript level of HO-1, another marker of oxidative stress, suggesting that Mg deficiency-induced Myod expression does not result from oxidative stress. Furthermore, oxidative stress induced by hydrogen peroxide did not increase Myod expression, whereas the expression of Myod, myogenin and Myhc IIb was decreased by oxidative stress from the initial phase of differentiation. The effects of Mg deficiency depended on the stages of myogenesis; myoblast culture in Mg-deficient differentiation medium did not affect the expression of Myod and Myhc IIb. The present study revealed stage-dependent effects of Mg deficiency on myogenesis.